Characterization of a leukocyte-derived endogenous mediator responsible for increased plasma fibrinogen.
Fibrinogen has been the plasma protein most frequently studied after tissue injury. This report presents evidence that leukocytic endogenous mediator (LEM) from macrophages promotes fibrinogen synthesis. LEM has a molecular weight of 13,000-16,000, an isoelectric point (pI) at pH 7.3, is heat labile, and is inactivated by trypsin or sulfhydryl reactive agents. LEM not only promotes increased synthesis of acute phase proteins, but also causes increased neutrophilia and alterations in metal metabolism. There is considerable evidence that LEM may be the same protein as endogenous pyrogen and Interleukin 1 (IL-1). There was no increase in plasma fibrinogen when endotoxin was injected in C3H/HeJ mice; however, this strain of mice responded the same as normal mice to injections of LEM. This provides further evidence that LEM is the endogenous mediator for acute phase protein synthesis during tissue injury. The half-life of LEM is still circulation following its iv injection into rats was less than 10 minutes. There is still considerable doubt about the mechanism LEM uses in promoting increased hepatocyte synthesis of fibrinogen. Some evidence indicates a direct action of LEM upon the hepatocyte, whereas other data suggest an indirect role through other mediators or the central nervous system. In addition to LEM with pI of 7.3, there are proteins with a pI near 5 that will increase plasma fibrinogen. These proteins also have a molecular weight between 13,000 to 16,000 but do not have essential sulfhydryl groups. These proteins also have pyrogenic and IL-1 activities. LEM shows a limited amount of species specificity. For example, the pI 7 LEM prepared from human monocytes or rabbit peritoneal leukocytes will increase plasma fibrinogen in rats, mice, and rabbits; but the pI 5 LEM from rabbits is inactive in rats.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005334:Fever / Q000097:blood; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood; D007375:Interleukin-1; D008970:Molecular Weight; D011506:Proteins / Q000302:isolation & purification / Q000502:physiology*; D011749:Pyrogens / Q000502:physiology; D013045:Species Specificity
D007375:Interleukin-1; D011506:Proteins; D011749:Pyrogens; C008270:leukocyte endogenous mediator; D005340:Fibrinogen